Guided Treatment Based on Mini-PDX in Metastatic Triple Negative Breast Cancer

NCT04745975 | Unknown Phase 2

• 1 other identifier: GUMPTION
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Triple-negative breast cancer constitutes 15-20% of cases of breast cancer and is defined by the absence of estrogen receptors, progesterone receptors, and overexpression or gene amplification of HER2. Although the addition of immune checkpoint inhibitors could improve the outcome of patients with metastatic triple-negative breast cancer (mTNBC), chemotherapy has been the standard of care for systemic treatment for patients with mTNBC. Prognoses remain poor, with reported median overall survival estimates of approximately 18 months or less with available treatments. A meta-analysis of seven clinical trials showed that the median objective response rate (ORR) of second or later line of chemotherapy in mTNBC was only 11%. Patient-derived xenograft (PDX) tumor model, which preserves the histologic and genetic characteristics of patients' tumors, has shown its predictive value of clinical outcomes and are used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. However, long time period and low success rate has limited its application in clinical practice. Mini patient derived xenograft (miniPDX) offers an effective alternative as it only takes about 7 days for drug sensitivity test and could thus provide guidance for prompt personalized treatment for each patient. Thus, the investigators conduct this single-center, prospective, randomized controlled clinical study to investigate the efficacy of guided treatment based on Mini-PDX in patients with metastatic refractory triple negative breast cancer.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  To compare the Objective Response Rate (ORR) of patients who recieve persionalized treatment based on mini-PDX model with ORR of patients who receive Treatment of Physician's Choice (TPC). ORR is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1. ORR will be calculated based on the Investigator assessment of response. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

  Through study completion, an expected average of 1 year

Secondary Outcomes (3)

• Overall Survival

  Through study completion, an expected average of 1 year

• Progression-Free Survival

  Through study completion, an expected average of 1 year

• Adverse events

  Through study completion, an expected average of 1 year

Study Arms (2)

Personalized treatment guided by Mini-PDX

EXPERIMENTAL

The tumor tissue is used for drug sensitivity test by Mini-PDX, and acquiring the genetic information by RNA-sequence. Patients with mTNBC will receive personalized treatment guided by the experimental results of mini-PDX and RNA sequencing.

Drug: Personalized treatment guided by mini-PDX and RNA sequencing

Treatment of Physician's Choice (TPC)

ACTIVE COMPARATOR

TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.

Drug: Nab paclitaxel; Drug: Eribulin; Drug: Vinorelbine; Drug: Gemcitabine; Drug: Capecitabine

Interventions

Personalized treatment guided by mini-PDX and RNA sequencing DRUG

Personalized treatment guided by mini-PDX and RNA sequencing

Personalized treatment guided by Mini-PDX

Nab paclitaxel DRUG

Nab-paclitaxel 125 mg/m2，ivgtt，d1, 8, 15, q4w

Treatment of Physician's Choice (TPC)

Eribulin DRUG

Eribulin 1.4 mg/m2, d1,8 q3w

Treatment of Physician's Choice (TPC)

Vinorelbine DRUG

Vinorelbine 25mg/m2 d1,8, q3w

Treatment of Physician's Choice (TPC)

Gemcitabine DRUG

Gemcitabine 1000 mg/m2, d1,8, q3w

Treatment of Physician's Choice (TPC)

Capecitabine DRUG

Capecitabine 1250 mg/m2 bid po

Treatment of Physician's Choice (TPC)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Women aged 18-70 years;
• \) an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• \) Estimated lifetime is ≥ 3 months;
• \) Histopathologically confirmed recurrent (unresectable) or metastatic triple-negative breast cancer; ER and PR negative is defined as ER \<1% positive, PR \<1% positive. HER-2 negative is defined as HER-2 (-) or (1+) by immunohistochemistry, HER-2 (2+) must be tested by FISH with negative result, HER-2 (1+) (1+), FISH is optional and negative;
• \) Have at least one measurable target lesion according to RECIST 1.1 criteria;
• \) Biopsy of the tumor lesion and the specimen passes laboratory quality control;
• \) A minimum of 2 prior cytotoxic chemotherapy regimens (including at least one line of platinum-containing regimen) in metastatic settings are required prior to enrollment in this trial;
• \) Adequate organ function, i.e. meeting the following criteria.
• Hb ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 109 /L; PLT ≥ 75 × 109 /L.
• Liver function: total bilirubin TBIL ≤ 1.5×ULN (upper limit of normal); ALT and AST ≤ 3×ULN.
• serum Cr ≤ 1.5×ULN.
• \) Subjects voluntarily joined the study, signed the informed consent form, were compliant and cooperated with the follow-up.

You may not qualify if:

• ）Pregnancy or lactation；
• ）History of autoimmune disease；
• ）Anticancer- and radiation therapy-related toxicities have not resolved or downgraded to Grade 1 or less;
• \) Symptomatic central nervous system (CNS) disease;
• \) Previous treatment of Immune checkpoint inhibitors;
• \) History of other malignancies within the past five years, with the exception of cured non-malignant melanoma of the skin and carcinoma in situ of the cervix.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Sequence Analysis, RNA; Taxes; eribulin; Vinorelbine; Gemcitabine; Capecitabine

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques; Economics; Health Care Economics and Organizations; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Xichun Hu, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xichun Hu, M.D.

CONTACT

021-54561523; xchu2009@hotmail.com

Jian Zhang, M.D.

CONTACT

021-54561523; syner2000@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Medical Oncology

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 9, 2021
• Study Start: February 1, 2021
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2023
• Last Updated: April 20, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)